# Association between interleukin-27 and suicidal ideation: a Mendelian randomization analysis and peripheral blood experimental study

## TL;DR

This study finds that the cytokine IL-27 is genetically and biologically linked to suicidal ideation in people with depression, suggesting it could be a useful biomarker for assessing suicide risk.

## Contribution

The study identifies IL-27 as a novel genetic and biological marker for suicidal ideation in major depressive disorder.

## Key findings

- Genetic analysis shows IL-27 has a positive association with suicidal ideation.
- High-risk individuals have elevated peripheral IL-27 levels compared to low-risk individuals.
- TRAIL shows a negative genetic association with suicidal ideation.

## Abstract

Suicide is a leading global cause of mortality, with major depressive disorder (MDD) contributing significantly. Neuroimmune mechanisms, particularly inflammation, are increasingly recognized in the pathophysiology of depression and suicidal ideation. This study investigated the relationship between inflammatory cytokines and suicidal ideation in patients with MDD.

A two sample Mendelian randomization analysis using Genome-Wide Association Study data was performed to evaluate the associations between 16 inflammatory cytokines and suicidal ideation. Then the patients with MDD, stratified by suicidal ideation severity were assessed for peripheral cytokine levels (interleukin [IL])-2, IL-4, IL-6, IL-10, interferon-gamma [IFN-γ], IL-17, IL-12, IL-27, and tumor necrosis factor-α) using flow cytometry and enzyme-linked immunosorbent assay.

MR analysis revealed significant associations of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and IL-27 with negative and positive effects, respectively. Individuals with high suicide risk exhibited elevated IL-27, IL-12, IFN-γ and IL-4 compared with low suicide risk.

There are genetic associations between IL-27 and suicidal ideation, which is biologically corroborated by elevated peripheral IL-27 levels in high-risk suicidal individuals, highlighting its potential as a clinically viable biomarker for assessing suicidal risk in depressive patients.